Amgen, Entera to Partner on Oral Drugs for Inflammatory Disease, Other “Serious” Illnesses

Amgen will partner with Entera Bio to develop new treatments for inflammatory disease and other serious illnesses using the oral drug discovery platform of Entera, it said today, through a collaboration that could generate more than $270 million for the Israeli biopharma.

Entera said it will use its platform to develop oral formulations for one preclinical large molecule program that Amgen has selected. The company did not detail that program—except to say that it is “very different” from the oral human parathyroid hormone analog Oral PTH 1-34 formulation applied in both clinical programs in Entera’s pipeline—”highlighting the broad applicability of our technology,” Entera CEO Phillip Schwartz, Ph.D., said in a statement.

Amgen holds an option to include up to two additional programs in the collaboration.

“This collaboration is an important validation of our platform technology,” Dr. Schwartz added.

Entera says its platform uses a combination of a synthetic absorption enhancer or “carrier molecule” to facilitate the enhanced absorption of large molecules, and protease inhibitors to prevent enzymatic degradation, protecting the large molecule from digestion.

The platform is designed to address two challenges to oral delivery of large-molecule drugs: Poor absorption into the bloodstream due to enzymatic degradation within the gastrointestinal tract, and poor permeability through the intestinal wall.

Entera’s pipeline includes EB612, which applies PTH 1-34 to treat hypoparathyroidism and for which a Phase IIa trial (NCT03516773) is “active, not recruiting” patients as of today. Also in the pipeline is EB613, which applies PTH 1-34 to treat osteoporosis, and for which a Phase I trial has been completed, Entera stated on its website.

Under its research collaboration and license agreement with Amgen, Entera will receive an undisclosed “modest” initial technology access fee from Amgen, and has agreed to oversee preclinical development at Amgen’s expense.

Amgen has agreed to pay Entera up to $270 million in payments tied to achieving clinical and commercial milestones and Amgen deciding to move all programs forward, as well as tiered royalties up to mid-single digits.

Amgen has agreed to oversee clinical development, manufacturing, and commercialization of any programs resulting from the collaboration, Entera added.

Entera will retain all intellectual property rights to its drug delivery technology, which under this collaboration will be licensed to Amgen exclusively for Amgen’s nominated drug targets. Amgen will retain all rights to its large molecules and any subsequent improvements.

Inflammation is one of Amgen’s six therapeutic areas of focus; the other five are cardiovascular disease, oncology, bone health, neuroscience, and nephrology.

Amgen’s inflammation pipeline is led by two Phase III programs. One is a potential new indication for its marketed drug Enbrel® (etanercept), as a monotherapy for psoriatic arthritis treatment and for maintaining remission of rheumatoid arthritis.

The other is the asthma program for tezepelumab (formerly AMG 157), a thymic stromal lymphopoietin (TSLP) inhibitor being developed with AstraZeneca under a partnership launched in 2012. In September, the FDA granted tezepelumab its Breakthrough Therapy designation in patients with severe asthma, without an eosinophilic phenotype, who are receiving inhaled corticosteroids/long-acting beta2-agonists with or without oral corticosteroids and additional asthma controllers.

Tezepelumab is also one of Amgen’s three Phase II development programs (for atopic dermatitis). The other two are AMG 557, an ICOS ligand inhibitor being investigated for primary Sjögren’s syndrome; and AMG 714, a human monoclonal antibody that binds to Interleukin-15 (IL-15), was re-acquired in November 2017 from Celimmue, and is being studied for celiac disease.

Amgen has three Phase I inflammation programs: AMG 570, a bispecific antibody-peptide conjugate that targets BAFF and ICOS ligand, and is being studied for systemic lupus erythematosus; AMG 592, an IL-2 mutein Fc fusion protein being developed for unspecified inflammatory diseases; and AMG 966, a monoclonal antibody being investigated for the treatment of inflammatory bowel diseases (Crohn’s disease and ulcerative colitis).